Hypothalamic Peptides in the Control of Alcohol Intake

下丘脑肽控制酒精摄入量

基本信息

  • 批准号:
    8577115
  • 负责人:
  • 金额:
    $ 36.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-07-01 至 2015-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Hypothalamic systems known to have a primary role in food intake are also important in controlling the consumption of ethanol. Our previous studies have shown that peptide systems in the hypothalamic paraventricular nucleus (PVN) become engaged in stimulating ethanol intake, which in turn feeds back to further increase the expression of these same peptides. More recently, we have begun to examine the perifornical lateral hypothalamus (PFLH) and have identified marked differences from the PVN in the functioning of the peptides in this area as they relate to ethanol consumption. Building on this information and the extensive preliminary results developed from it, we plan to test in Sprague-Dawley rats the novel idea that hypothalamic peptides expressed in the PFLH, specifically orexin (OX) and melanin-concentrating hormone (MCH), have different functions from those in the PVN, enkephalin (ENK) and galanin (GAL), in enhancing ethanol drinking. Whereas PFLH peptides initiate episodes of ethanol intake, PVN peptides prolong periods of ethanol consumption. Aim 1 is to examine the behavioral functions of these peptides in the PFLH and PVN, as they trigger or sustain ethanol intake, interact in this process, and respond in turn to the changes in ethanol consumption and corresponding blood ethanol concentrations. Aim 2 is to determine whether these peptides are disturbed in animals predicted to be at risk for overconsuming ethanol based on different behavioral- and bio-markers. We will test the hypothesis that animals at risk have disturbed expression of peptides in the hypothalamus prior to learning to drink ethanol or before an anticipated, large bout of ethanol consumption. This aim will also examine ENK in the mesolimbic dopamine (DA) system, which is intimately involved in controlling the ingestion of rewarding substances. Aim 3 is to determine whether animals at risk for overconsuming ethanol, due to prenatal exposure, exhibit disturbances in in utero development of these peptide systems that cause increased expression of the peptides and long-term overconsumption in the offspring. Lastly, Aim 4 is to investigate the hypothesis that neurochemical feedback signals to the PFLH compared to the PVN, via DA, -aminobutyric acid (GABA), glutamate (GLUT) and ENK inputs, have opposite effects on the local peptide systems that determine how they influence ethanol drinking behavior. As pharmacological therapies used to treat alcoholism act in part through these neurochemical control systems, we will test whether medications more effective in treating relapse in humans, seen as analogous to initiation of drinking, are working through the PFLH peptide systems; in contrast, those therapies more effective in treating ongoing excessive consumption, analogous to prolongation of drinking, are working through the PVN peptide systems. Collectively, these 4 Aims will provide significant, new information regarding the involvement and regulation of two hypothalamic areas and their local peptide systems, as they control patterns of ethanol drinking, contribute to alcohol abuse, and mediate the actions of medications in treating relapse and ongoing drinking in humans.
描述(由申请人提供):已知在食物摄入中具有主要作用的下丘脑系统对于控制乙醇的消耗也很重要。我们先前的研究表明,下丘脑旁脑室核(PVN)中的肽系统参与刺激乙醇的摄入量,进而进食以进一步增加这些相同肽的表达。最近,我们开始检查肌部下丘脑(PFLH),并确定了与乙醇消耗相关的肽在该区域的功能中与PVN的明显差异。我们计划在Sprague-Dawley大鼠中测试这些信息和广泛的初步结果,即在PFLH中表达的下丘脑肽,特别是Orexin(OX)(OX)和黑色素浓缩激素(MCH),其功能与PVN,Enkephalin(Enkephalin(Enkephalin)(Enkephalin(Galan)和Galanin(Galan)和Galanin(Galan)(Galan)(Galan)(Galan)中,它们具有不同的功能。而PFLH肽会引发乙醇摄入的发作,而PVN肽延长了乙醇消耗的时期。目标1是在PFLH和PVN中检查这些肽在触发或维持乙醇摄入量,在此过程中相互作用时的行为功能,并反过来响应乙醇消耗和相应的血液乙醇浓度的变化。 AIM 2是确定这些肽是否受到预测的动物的干扰,该动物的风险过度基于不同的行为和生物标记。我们将检验以下假设:在学会喝乙醇或预期的大量乙醇消耗之前,有风险的动物在下丘脑中扰乱了肽的表达。该目标还将检查中唇多巴胺(DA)系统中的ENK,该系统与控制奖励物质的摄入密切相关。 AIM 3是确定由于产前暴露引起的过度耗尽乙醇的风险是否会在这些肽系统的子宫内发育中出现干扰,从而导致肽的表达增加并在后代中长期过度消费。最后,目标4是研究与PVN相比,与PVN相比,通过DA, - 氨基丁酸(GABA),谷氨酸(GLUT)和ENK输入对PVN的神经化学反馈信号的假设具有相反的作用,对局部肽系统的影响相反,从而决定如何影响乙醇饮酒行为。正如用于治疗酒精中毒的药理学疗法通过这些神经化学控制系统的一部分作用,我们将测试药物在治疗人类复发方面是否更有效,被视为类似于饮酒的开始,正在通过PFLH肽系统进行工作。相比之下,这些疗法在治疗持续的过度消费方面(类似于饮酒的延长)正在通过PVN肽系统进行工作。总的来说,这四个目标将提供有关两个下丘脑区域及其当地肽系统的参与和调节的重要新信息,因为它们控制了乙醇饮酒的模式,有助于酒精滥用,并调解药物在治疗复发和人类中持续饮酒中的药物作用。

项目成果

期刊论文数量(0)
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SARAH F LEIBOWITZ其他文献

SARAH F LEIBOWITZ的其他文献

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{{ truncateString('SARAH F LEIBOWITZ', 18)}}的其他基金

Mechanisms underlying diverse effects of low-dose embryonic ethanol on development and function of hypocretin/orexin neurons
低剂量胚胎乙醇对下丘脑分泌素/食欲素神经元发育和功能的多种影响的机制
  • 批准号:
    10559612
  • 财政年份:
    2020
  • 资助金额:
    $ 36.88万
  • 项目类别:
Mechanisms underlying diverse effects of low-dose embryonic ethanol on development and function of hypocretin/orexin neurons
低剂量胚胎乙醇对下丘脑分泌素/食欲素神经元发育和功能的多种影响的机制
  • 批准号:
    9886626
  • 财政年份:
    2020
  • 资助金额:
    $ 36.88万
  • 项目类别:
Mechanisms underlying diverse effects of low-dose embryonic ethanol on development and function of hypocretin/orexin neurons
低剂量胚胎乙醇对下丘脑分泌素/食欲素神经元发育和功能的多种影响的机制
  • 批准号:
    10350666
  • 财政年份:
    2020
  • 资助金额:
    $ 36.88万
  • 项目类别:
Excess ethanol drinking after prenatal exposure to ethanol: chemokine signaling and orexigenic neuropeptides
产前接触乙醇后过量饮酒:趋化因子信号传导和促食欲神经肽
  • 批准号:
    9899907
  • 财政年份:
    2016
  • 资助金额:
    $ 36.88万
  • 项目类别:
Excess ethanol drinking after prenatal exposure to ethanol: chemokine signaling and orexigenic neuropeptides
产前接触乙醇后过量饮酒:趋化因子信号传导和促食欲神经肽
  • 批准号:
    9082977
  • 财政年份:
    2016
  • 资助金额:
    $ 36.88万
  • 项目类别:
Excess ethanol drinking after prenatal exposure to ethanol: chemokine signaling and orexigenic neuropeptides
产前接触乙醇后过量饮酒:趋化因子信号传导和促食欲神经肽
  • 批准号:
    9257255
  • 财政年份:
    2016
  • 资助金额:
    $ 36.88万
  • 项目类别:
Mechanisms of nicotine and alcohol use: Focus on in utero exposure to dietary fat
尼古丁和酒精使用的机制:关注子宫内膳食脂肪的暴露
  • 批准号:
    8438408
  • 财政年份:
    2012
  • 资助金额:
    $ 36.88万
  • 项目类别:
Mechanisms of nicotine and alcohol use: Focus on in utero exposure to dietary fat
尼古丁和酒精使用的机制:关注子宫内膳食脂肪的暴露
  • 批准号:
    8303789
  • 财政年份:
    2012
  • 资助金额:
    $ 36.88万
  • 项目类别:
Hypothalamic Peptides in the Control of Alcohol Intake
下丘脑肽控制酒精摄入量
  • 批准号:
    8374129
  • 财政年份:
    2001
  • 资助金额:
    $ 36.88万
  • 项目类别:
Hypothalamic Peptides in the Control of Alcohol Intake
下丘脑肽控制酒精摄入量
  • 批准号:
    8204432
  • 财政年份:
    2001
  • 资助金额:
    $ 36.88万
  • 项目类别:

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